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Glutamate dehydrogenase 1 (GLUD1), a key enzyme in glutaminolysis, is frequently overexpressed in malignancies. Post-translational modifications (PTMs) are crucial for regulating protein function and tumor progression. However, the PTMs of GLUD1, particularly arginine methylation, remain unexplored. Here we report that protein arginine methyltransferase 7 (PRMT7) mediates monomethylation of GLUD1 at arginine 76 (R76), enhancing its protein stability by antagonizing ubiquitin-dependent degradation. Moreover, high glucose destabilizes GLUD1 via the PI3K\/Akt pathway. Mechanistically, AKT1 phosphorylates PRMT7 at threonine 73 (T73) and promotes its activity to stabilize GLUD1 by increasing its methylation and reducing ubiquitination. Clinical analysis reveals that elevated GLUD1, PRMT7, and meGLUD1(R76) levels correlate with tumor progression in gastric cancer. In xenograft models, PRMT7 inhibitor SGC3027 combined with chemotherapeutic drugs docetaxel (DTX) synergistically suppresses tumor growth. Collectively, this study identifies the AKT1-PRMT7-GLUD1 axis as a key regulatory pathway in gastric cancer, and highlights its potential as a therapeutic target.<\/jats:p>","DOI":"10.1038\/s41419-026-08601-8","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T22:15:50Z","timestamp":1774390550000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["AKT1 phosphorylates PRMT7 to promote GLUD1 methylation and gastric cancer progression"],"prefix":"10.1038","volume":"17","author":[{"given":"Ziyi","family":"Cui","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2639-8726","authenticated-orcid":false,"given":"Hongchen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoben","family":"Liang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siyao","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0308-6562","authenticated-orcid":false,"given":"Zhen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4820-3125","authenticated-orcid":false,"given":"Lei","family":"Lv","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2750-5466","authenticated-orcid":false,"given":"Yanping","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"8601_CR1","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.tibs.2010.05.003","volume":"35","author":"DR Wise","year":"2010","unstructured":"Wise DR, Thompson CB. 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